Nebulette is a 116.4 kDa protein composed of 1014 amino acids.[5][6] As a member of the nebulin family of proteins, nebulette is characterized by 35 amino acid stretches of ‘‘nebulin repeats’’, which are actin binding domains containing a conservedSDxxYK motif.[7] Like nebulin, nebulette has an acidic region with unknown structure at its N-terminus, and a serine-rich region adjacent to anSH3 domain at its C-terminus.[8] Though nebulette shares structural features with nebulin, nebulin is expressed preferentially inskeletal muscle and has an enormous size (600-900 kDa), while nebulette is expressed incardiac muscle atZ-disc regions and is significantly smaller (roughly 1/6 of the size).[9] Nebulette interacts withactin,tropomyosin,alpha-actinin.[10]Xin, andXIRP2.[11]
Nebulette was identified in 1995 by Moncman and Wang using primary cultures of chicken embryoniccardiomyocytes byimmunoprecipitations with certain anti-nebulinmonoclonal antibodies.[12] Normal expression of nebulette is essential for the assembly andcontractile function ofmyofibrils.[13] Specifically, nebulette appears to regulate the stability and length of actin thin filaments, as well as beating frequencies of cardiomyocytes; reduction of full-length nebulette protein in cardiomyocytes resulted in reduced thin filament lengths, depressed beating frequencies and loss of thin filament regulatory proteinstroponin I andtropomyosin.[14][15]
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle".Cell Motility and the Cytoskeleton.32 (3):205–225.doi:10.1002/cm.970320305.PMID8581976.
^Moncman CL, Wang K (1995). "Nebulette: a 107 kD nebulin-like protein in cardiac muscle".Cell Motility and the Cytoskeleton.32 (3):205–225.doi:10.1002/cm.970320305.PMID8581976.
^Moncman CL, Wang K (February 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function".Experimental Cell Research.273 (2):204–218.doi:10.1006/excr.2001.5423.PMID11822876.
^Bonzo JR, Norris AA, Esham M, Moncman CL (November 2008). "The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere".Experimental Cell Research.314 (19):3519–3530.doi:10.1016/j.yexcr.2008.09.001.PMID18823973.
^Moncman CL, Wang K (February 2002). "Targeted disruption of nebulette protein expression alters cardiac myofibril assembly and function".Experimental Cell Research.273 (2):204–218.doi:10.1006/excr.2001.5423.PMID11822876.
^Arimura T, Nakamura T, Hiroi S, Satoh M, Takahashi M, Ohbuchi N, et al. (November 2000). "Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy".Human Genetics.107 (5):440–451.doi:10.1007/s004390000389.PMID11140941.S2CID4564490.
